This research project is designed to investigate the replication of enveloped RNA viruses in mouse peritoneal macrophages. The major emphasis will be placed on studies with lactic dehydrogenase virus (LDV) - a virus that causes a persistent, non-cytopathic infection in mice, appears to replicate only in macrophages, and causes diverse effects on the animal's immune system. Our specific objectives are: (1) to identify the steps in LDV replication in permissive cells and then determine which of these are prevented in non-permissive hosts; (2) to examine persistent infection by LDV and, in particular, characterize defective-interfering particles which may accumulate; and (3) to initiate studies on viral replication in mice genetically-altered to flaviviruses. Sensitivity or resistance may reside in macrophages and may be related to the generation of defective-interfering particles. We shall examine these mice, and cells obtained from them, for differences in their response to LDV.